What are the treatment options for a young adult with a potential diagnosis of aggressive Hodgkin's lymphoma, presenting with newly enlarged lymph nodes in the groin and behind the ear?

Urgent Diagnostic Workup and Treatment for Suspected Hodgkin's Lymphoma with Multi-Site Lymphadenopathy

This patient requires immediate excisional lymph node biopsy of the most accessible enlarged node (groin or post-auricular) followed by comprehensive staging with CT neck/chest/abdomen/pelvis, PET-CT, bone marrow biopsy, and laboratory evaluation to determine disease stage and risk stratification before initiating treatment. 1

Immediate Diagnostic Steps

Tissue Diagnosis (First Priority)

• Perform excisional lymph node biopsy of either the groin or post-auricular node—whichever is most accessible—to obtain sufficient tissue for both formalin-fixed and fresh frozen samples 1
• The biopsy must provide enough material for immunohistochemistry (CD15+/CD30+/CD20- for classical HL) and WHO classification 1
• Core needle biopsy is inadequate except in emergency situations requiring immediate treatment 1

Mandatory Staging Workup (Immediately After Diagnosis)

• CT scan with contrast of neck, chest, abdomen, and pelvis to identify all sites of lymph node involvement 1
• PET-CT scan for accurate initial staging and baseline assessment 1, 2
• Bone marrow biopsy (unilateral) to exclude marrow involvement, particularly important given B-symptoms or advanced stage disease 1
• Complete blood count, ESR, LDH, liver enzymes, albumin, renal function, and uric acid 1
• Screening for HBV, HCV, and HIV is mandatory before treatment 1

Pre-Treatment Assessment

• Cardiac function testing (echocardiogram with left ventricular ejection fraction) before anthracycline-based chemotherapy 1, 3
• Pulmonary function tests before bleomycin exposure 1, 3
• Reproductive counseling for young adults regarding fertility preservation before chemotherapy 1
• Thyroid function (TSH) baseline measurement 1

Risk Stratification and Stage Assignment

The presence of lymph nodes in both groin and post-auricular regions suggests at minimum Stage II disease (two or more lymph node regions on same side of diaphragm), but could represent Stage III (both sides of diaphragm) or Stage IV if extranodal involvement exists 1

Critical Risk Factors to Assess

• Large mediastinal mass (>1/3 maximum chest diameter on chest X-ray) 1
• Extranodal disease (involvement of organs beyond lymph nodes) 1, 2
• Elevated ESR (>50 mm/h without B-symptoms; >30 mm/h with B-symptoms) 1
• Three or more involved lymph node areas 1
• B-symptoms (fever >38°C, night sweats, >10% weight loss in 6 months) 1

Treatment Algorithm Based on Stage and Risk

If Early Favorable Stage (Stage I-II, No Risk Factors)

• 2 cycles of ABVD chemotherapy followed by 30 Gy involved-field radiotherapy 1, 3
• ABVD consists of doxorubicin, bleomycin, vinblastine, and dacarbazine given every 14 days 3, 4, 5

If Intermediate Stage (Stage I-II with ≥1 Risk Factor)

• 4 cycles of ABVD chemotherapy followed by 30 Gy involved-site radiotherapy 1, 2, 3
• This achieves tumor control rates of 85-90% at 5 years with overall survival exceeding 90% 2, 3
• For patients <60 years eligible for intensive treatment, consider 2 cycles of escalated BEACOPP followed by 2 cycles of ABVD and 30 Gy radiotherapy 2

If Advanced Stage (Stage III-IV or Stage IIB with Large Mediastinal Mass/Extranodal Disease)

• 6 cycles of ABVD chemotherapy is the standard approach 3, 6, 7, 8
• Alternative: 4-6 cycles of escalated BEACOPP demonstrates superior disease-free survival and overall survival compared to ABVD in advanced stages 3, 9
• Radiotherapy reserved for consolidation of bulky sites or residual PET-positive disease 1

Critical Treatment Considerations

Age-Specific Modifications

• For patients >60 years: Use ABVD-based chemotherapy but discontinue bleomycin after cycle 2 due to increased pulmonary toxicity risk 3

Response Assessment During Treatment

• PET-CT after 2-4 cycles to assess early response and guide treatment modifications 1, 6, 7, 8
• PET-CT at treatment completion to confirm complete remission 2, 6, 7, 8

Common Pitfalls to Avoid

• Never reduce chemotherapy doses due to hematological toxicity in curative-intent treatment; instead use prophylactic growth factors (G-CSF) 1
• Do not perform staging laparotomy—it is obsolete and not recommended 1
• Avoid fine needle aspiration for diagnosis—it provides insufficient tissue for accurate classification 1

If Refractory or Relapsed Disease

• High-dose chemotherapy followed by autologous stem cell transplant is standard of care for relapsed disease after initial therapy 9, 6, 7, 10, 8
• For patients failing autologous transplant: consider brentuximab vedotin, anti-PD-1 antibodies (nivolumab/pembrolizumab), non-myeloablative allogeneic transplant, or clinical trial enrollment 6, 7, 10, 8

Long-Term Surveillance

• Monitor for late effects including secondary malignancies, cardiovascular disease, and thyroid dysfunction 1, 2
• Thyroid function testing at 1,2, and 5 years post-treatment if neck irradiation was performed 1
• Blood count and LDH at 3,6,12, and 24 months, then as clinically indicated 1